Erdafitinib Wins EU Approval for FGFR3+ Unresectable, Metastatic Urothelial Carcinoma

Yohann Loriot, MD, PhD

The European Commission (EC) has approved erdafitinib (Balversa) monotherapy for the treatment of adult patients with unresectable or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations who have previously received at least 1 prior line of therapy containing a PD-1 or PD-L1 inhibitor in the metastatic setting.¹

The approval was based on data from cohort 1 of the phase 3 THOR study (NCT03390504), which showed erdafitinib reduced the risk of death by 36% vs chemotherapy (HR, 0.64; 95% CI, 0.44-0.93; P = .0050). Patients treated with erdafitinib (n = 136) experienced a median overall survival (OS) of 12.1 months vs 7.8 months in patients treated with chemotherapy (n = 130).

Additionally, patients treated with erdafitinib achieved a median progression-free survival (PFS) of 5.6 months compared with 2.7 for those treated with chemotherapy (HR, 0.58; 95% CI, 0.41-0.82; P = .0002). Erdafitinib generated a confirmed overall response rate (ORR) of 35.3% vs 8.5% with chemotherapy.

“Bladder cancer is one of Europe’s most common cancers and the need for innovative treatment options for people living with unresectable or metastatic urothelial carcinoma remains high,” Yohann Loriot, MD, PhD, of the Institut Gustave Roussy and Université of Paris-Saclay, in Villejuif, Paris, stated in a news release. “Erdafitinib is a novel, targeted therapy that has been shown to significantly improve OS and PFS for patients with FGFR3 alterations, who, until now, have had limited options available.”

The pan-FGFR TKI received full approval from the FDA in January 2024 for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations whose disease has progressed on or after at least 1 prior line of systemic therapy.² This regulatory decision was also based on data from cohort 1 of THOR.

The randomized, open-label study evaluated the efficacy and safety of erdafitinib and enrolled patients with unresectable or metastatic urothelial carcinoma harboring selected FGFR genetic alterations. Patients were required to have disease progression on or after 1 or 2 prior lines of treatment.¹

In cohort 1, eligible patients who received prior treatment with a PD-1 or PD-L1 inhibitor were randomly assigned 1:1 to receive erdafitinib or investigator’s choice of chemotherapy consisting of docetaxel or vinflunine. In cohort 2, patients who had not received a prior checkpoint inhibitor were randomly assigned to receive erdafitinib or pembrolizumab (Keytruda). Treatment continued until disease progression, intolerable toxicity, withdrawal of consent, or decision by investigator to discontinue treatment.

Notably, following the interim efficacy analysis, based on the recommendation of the independent data safety monitoring committee, patients assigned to chemotherapy were allowed to receive erdafitinib as crossover therapy.

The primary end point of the study was OS. Secondary endpoints included PFS, ORR, duration of response, patient-reported outcomes, safety, and pharmacokinetics.

Regarding safety in cohort 1, 13.3% of patients who received erdafitinib experienced serious treatment-related adverse effects (TRAEs) compared with 24.1% of patients treated with chemotherapy. Additionally, 45.9% of patients treated with the FGFR inhibitor had grade 3 or higher AEs vs 46.4% for those given chemotherapy. TRAEs led to treatment discontinuation in 8.1% of patients in the experimental arm vs 13.4% of patients treated with chemotherapy. One patient who received erdafitinib and 6 patients given chemotherapy had TRAEs that led to death.

“The EC approval of erdafitinib reflects our unwavering commitment to transforming outcomes for people living with unresectable or metastatic urothelial carcinoma,” Kiran Patel, MD, vice president of Clinical Development, Solid Tumors, at Johnson and Johnson Innovative Medicine, noted in the news release. “We look forward to continuing our research and development efforts to bring new hope and improved outcomes to more patients in the future.”

References

1. European Commission approves Balversa (erdafitinib) for adult patients with unresectable or metastatic urothelial carcinoma. News release. Janssen-Cilag International NV. August 23, 2024. Accessed August 23, 2024. https://www.janssen.com/european-commission-approves-balversarv-erdafitinib-adult-patients-unresectable-or-metastatic
2. FDA approves erdafitinib for locally advanced or metastatic urothelial carcinoma. FDA. January 19, 2024. Accessed August 23, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-erdafitinib-locally-advanced-or-metastatic-urothelial-carcinoma